Pyridine is the parent ring system of a very large number of most important biologically active compounds. We propose to continue our studies in the development of new methods for the direct replacement of a nuclear hydrogen by desirable substituents in such six-membered heteroaromatic compounds, starting with the N-oxide or N-ylide of the compound. These new synthetic methods involve novel molecular rearrangements, and some make available in one step polycyclic compounds not readily synthesized by other means. This will provide very desirable synthetic tools for the medicinal chemist as well as making available a large number of new heterocyclic compounds whose possible medicinal activity will be determined. In addition, pyridinium sulfonylmethylene ylides will be used to introduce the function NuCH equals (Nu tripleton nucelophile) into alpha, beta-unsaturated activated systems. These will be built up into novel ring systems of potential biological activity. Where possible additional functional groups will be introduced to enhance biological activity.